Bisphenol A Analogues Inhibit Human and Rat 11β-Hydroxysteroid Dehydrogenase 1 Depending on Its Lipophilicity
Bisphenol A (BPA) analogues substituted on the benzene ring are widely used in a variety of industrial and consumer materials. However, their effects on the glucocorticoid-metabolizing enzyme 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) remain unclear. The inhibitory effects of 6 BPA analogues on t...
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MDPI AG
2023-06-01
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| author | Hong Wang Jianmin Sang Zhongyao Ji Yang Yu Shaowei Wang Yang Zhu Huitao Li Yiyan Wang Qiqi Zhu Renshan Ge |
| author_facet | Hong Wang Jianmin Sang Zhongyao Ji Yang Yu Shaowei Wang Yang Zhu Huitao Li Yiyan Wang Qiqi Zhu Renshan Ge |
| author_sort | Hong Wang |
| collection | DOAJ |
| description | Bisphenol A (BPA) analogues substituted on the benzene ring are widely used in a variety of industrial and consumer materials. However, their effects on the glucocorticoid-metabolizing enzyme 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) remain unclear. The inhibitory effects of 6 BPA analogues on the inhibition of human and rat 11β-HSD1 were investigated. The potencies of inhibition on human 11β-HSD1 were bisphenol H (IC<sub>50</sub>, 0.75 µM) > bisphenol G (IC<sub>50</sub>, 5.06 µM) > diallyl bisphenol A (IC<sub>50</sub>, 13.36 µM) > dimethyl bisphenol A (IC<sub>50</sub>, 30.18 µM) > bisphenol A dimethyl ether (IC<sub>50</sub>, 33.08 µM) > tetramethyl bisphenol A (>100 µM). The inhibitory strength of these chemicals on rat 11β-HSD1 was much weaker than that on the human enzyme, ranging from 74.22 to 205.7 µM. All BPA analogues are mixed/competitive inhibitors of both human and rat enzymes. Molecular docking studies predict that bisphenol H and bisphenol G both bind to the active site of human 11β-HSD1, forming a hydrogen bond with catalytic residue Ser170. The bivariate correlation of IC<sub>50</sub> values with LogP (lipophilicity), molecular weight, heavy atoms, and molecular volume revealed a significant inverse regression and the correlation of IC<sub>50</sub> values with ΔG (low binding energy) revealed a positive regression. In conclusion, the lipophilicity, molecular weight, heavy atoms, molecular volume, and binding affinity of a BPA analogue determine the inhibitory strength of human and rat 11β-HSD isoforms. |
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| last_indexed | 2024-03-11T01:34:46Z |
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| series | Molecules |
| spelling | doaj.art-fa321a5ab16e452b985f154f37bf9bdb2023-11-18T17:05:04ZengMDPI AGMolecules1420-30492023-06-012813489410.3390/molecules28134894Bisphenol A Analogues Inhibit Human and Rat 11β-Hydroxysteroid Dehydrogenase 1 Depending on Its LipophilicityHong Wang0Jianmin Sang1Zhongyao Ji2Yang Yu3Shaowei Wang4Yang Zhu5Huitao Li6Yiyan Wang7Qiqi Zhu8Renshan Ge9Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, ChinaDepartment of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, ChinaDepartment of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, ChinaDepartment of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, ChinaDepartment of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, ChinaDepartment of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, ChinaDepartment of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, ChinaDepartment of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, ChinaDepartment of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, ChinaDepartment of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, ChinaBisphenol A (BPA) analogues substituted on the benzene ring are widely used in a variety of industrial and consumer materials. However, their effects on the glucocorticoid-metabolizing enzyme 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) remain unclear. The inhibitory effects of 6 BPA analogues on the inhibition of human and rat 11β-HSD1 were investigated. The potencies of inhibition on human 11β-HSD1 were bisphenol H (IC<sub>50</sub>, 0.75 µM) > bisphenol G (IC<sub>50</sub>, 5.06 µM) > diallyl bisphenol A (IC<sub>50</sub>, 13.36 µM) > dimethyl bisphenol A (IC<sub>50</sub>, 30.18 µM) > bisphenol A dimethyl ether (IC<sub>50</sub>, 33.08 µM) > tetramethyl bisphenol A (>100 µM). The inhibitory strength of these chemicals on rat 11β-HSD1 was much weaker than that on the human enzyme, ranging from 74.22 to 205.7 µM. All BPA analogues are mixed/competitive inhibitors of both human and rat enzymes. Molecular docking studies predict that bisphenol H and bisphenol G both bind to the active site of human 11β-HSD1, forming a hydrogen bond with catalytic residue Ser170. The bivariate correlation of IC<sub>50</sub> values with LogP (lipophilicity), molecular weight, heavy atoms, and molecular volume revealed a significant inverse regression and the correlation of IC<sub>50</sub> values with ΔG (low binding energy) revealed a positive regression. In conclusion, the lipophilicity, molecular weight, heavy atoms, molecular volume, and binding affinity of a BPA analogue determine the inhibitory strength of human and rat 11β-HSD isoforms.https://www.mdpi.com/1420-3049/28/13/4894bisphenol analogglucocorticoid11β-hydroxysteroid dehydrogenase 1cortisoldocking analysisspecies difference |
| spellingShingle | Hong Wang Jianmin Sang Zhongyao Ji Yang Yu Shaowei Wang Yang Zhu Huitao Li Yiyan Wang Qiqi Zhu Renshan Ge Bisphenol A Analogues Inhibit Human and Rat 11β-Hydroxysteroid Dehydrogenase 1 Depending on Its Lipophilicity Molecules bisphenol analog glucocorticoid 11β-hydroxysteroid dehydrogenase 1 cortisol docking analysis species difference |
| title | Bisphenol A Analogues Inhibit Human and Rat 11β-Hydroxysteroid Dehydrogenase 1 Depending on Its Lipophilicity |
| title_full | Bisphenol A Analogues Inhibit Human and Rat 11β-Hydroxysteroid Dehydrogenase 1 Depending on Its Lipophilicity |
| title_fullStr | Bisphenol A Analogues Inhibit Human and Rat 11β-Hydroxysteroid Dehydrogenase 1 Depending on Its Lipophilicity |
| title_full_unstemmed | Bisphenol A Analogues Inhibit Human and Rat 11β-Hydroxysteroid Dehydrogenase 1 Depending on Its Lipophilicity |
| title_short | Bisphenol A Analogues Inhibit Human and Rat 11β-Hydroxysteroid Dehydrogenase 1 Depending on Its Lipophilicity |
| title_sort | bisphenol a analogues inhibit human and rat 11β hydroxysteroid dehydrogenase 1 depending on its lipophilicity |
| topic | bisphenol analog glucocorticoid 11β-hydroxysteroid dehydrogenase 1 cortisol docking analysis species difference |
| url | https://www.mdpi.com/1420-3049/28/13/4894 |
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